Clinicopathologic Features and Immune Cell Subtypes Analysis of Tumor-infiltrating Lymphocytes Rich Invasive Breast Carcinoma of No Special Type.

Tumor-infiltrating lymphocytes (TILs) rich invasive breast carcinoma no special type (IBC-NST) is an updated name introduced in the fifth edition WHO classification of breast tumors. Typical medullary breast carcinoma (MBC) represents one end of the spectrum of TILs-rich IBC-NST rather than a distinct morphologic subtype in the new category. A total of 42 cases of MBC and 180 cases of high-grade triple-negative breast cancer (TNBC) without medullary features were included. All samples were stained for CD20, CD4, CD8, and FoxP3 by immunohistochemistry staining. TILs infiltration was more prominent in the MBC tumor nests and in the stroma of high-grade TNBC without medullary features. The average stromal TILs percentage was 78.10% and 61.33%. MBC showed significantly lower numbers of lymphocytes expressing FoxP3 ( P < 0.001), no significant difference in the number of CD4 ( P = 0.154), CD8 ( P = 0.199), and a significantly higher CD8/FoxP3 ratio ( P < 0.001) than the other high-grade TNBC. MBC cases demonstrated less aggressive features such as lower TNM stage ( P = 0.031), smaller tumor size ( P = 0.010), and negative lymph node status ( P = 0.021) than the other high-grade TNBC. The 5-year disease-free survival and overall survival were significantly higher for MBC 82.50% and 85.00% compared with the other high-grade TNBC(54.49% and 58.68%). MBC is mostly triple-negative with higher nuclear atypia. Despite advanced staging based on cell morphology, it has low malignancy and a good prognosis. Differences in biological features and prognosis between MBC and high-grade TNBC without medullary features may be associated with the composition and function of TILs. Immune cell subtypes are complex in TILs-rich IBC-NST and deserve further investigation.

Clinicopathological significances of PLOD2, epithelial-mesenchymal transition markers, and cancer stem cells in patients with esophageal squamous cell carcinoma.

BACKGROUND: To examine the expression level of procollagen-lysine2-oxoglutarate 5-dioxygenase 2 (PLOD2) in esophageal squamous cell carcinoma (ESCC) and analyze its correlation with clinicopathological parameters, in order to explore the mechanism of PLOD2 in regulating invasion and metastasis of ESCC. METHODS: Immunohistochemistry was used to detect the expression level of PLOD2 in tumor tissues and paired adjacent tissues of 172 patients with ESCC, and the relationship between PLOD2 expression and clinicopathological parameters was analyzed. The deposition of collagen fibers in tumor was detected by Sirius red staining. The correlation between tumor stem cells and epithelial-mesenchymal transition (EMT) markers ZEB1 was analyzed by multivariate logistic regression. RESULTS: The expression level of PLOD2 in tumor tissues of patients with ESCC (70.35%, 121/172) was significantly higher than that in paired adjacent tissues (29.65%, 51/172; P < .01). The positive expression rate of PLOD2 in ESCC was related to T classification, lymph node metastasis, and pathological tumor node metastasis of a tumor. The expression rates of ZEB1, CD44, and CD133 in ESCC were correlated with T classification, lymph node metastasis and pathological tumor node metastasis. Scarlet red staining showed that collagen fiber deposition in ESCC tissues with high expression of PLOD2 was significantly higher than that in tissues with low expression of PLOD2 (P < .01). A positive correlation was observed between the expression of PLOD2 and CD133, PLOD2 and CD44, and PLOD2 and N-cadherin (P < .01). Moreover, a negative correlation was noted between the expression of PLOD2 and E-cadherin (P < .01). The combined expression of PLOD2 and ZEB1 were independent prognostic factors for the total survival time of patients with ESCC. CONCLUSION: PLOD2 is highly expressed in ESCC and is closely related to tumor invasion and metastasis. The mechanism of PLOD2 for promoting invasion and metastasis of ESCC may be related to activation of the EMT signaling pathway to promote EMT and tumor stem cell transformation.

The Effect and Mechanism of New Processing Method of Codonopsis pilosula on Endocrine Physique Index in Rats.

Objective: To explore the effect and mechanism of a new processing method of Codonopsis pilosula (CP) on the endocrine physique index in rats. Methods: The rats were randomly assigned into the control group, model group, CP group (3.75 g/kg crude drug), rice-fried CP group (3.75 g/kg crude drug), and honey-roasted CP group (3.75 g/kg), with 10 rats in each group. All rats were gavaged according to the body weight of 1 mL/100 g every morning for 3 weeks. The water extracts of different processed products of CP were given to the drug group, the blank group, and the model group which were given the same volume of normal saline during the experiment. The model group and each administration group were fed every other day and drank freely for 21 days, during which the weight was weighed every 2 days. The changes of the organ index; the contents of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), adrenocorticotropic hormone (ACTH), and cortisol (Cor); and the activity of sodium and potassium adenosine triphosphate (Na+K+-ATP) were measured by enzyme-linked immunosorbent assay (ELISA). The expression of aquaporin-1 (AQP1) and aquaporin-2 (AQP2) mRNA was detected by RT-PCR. Results: Effect on the organ index: the organ index of the control group, CP group, rice-fried group, and honey moxibustion group was higher compared to that of the model group, and the organ index of the honey moxibustion group was the highest (P < 0.05). The level of cAMP and the ratio of cAMP/cGMP in the model group were significantly higher compared to those of the control group (P < 0.05); CGMP in the model group decreased significantly (P < 0.05). Compared with the model group, the level of cAMP in the CP group, rice-fried group, and honey moxibustion group decreased significantly, while the ratio of cGMP and cAMP/cGMP increased significantly (P < 0.05). Compared with the CP group, rice-fried group, and honey moxibustion group, the level of cAMP and the ratio of cAMP/cGMP in the honey moxibustion group were lower compared to those in the other two groups, and the ratio of cGMP in the honey moxibustion group was higher compared to that in the other two groups (P < 0.05). The contents of ACTH and Cor in the model group were significantly higher compared to those in the control group (P < 0.05). Compared with the model group, the contents of ACTH and Cor in the CP group, rice-fried group, and honey moxibustion group were significantly lower compared to those in the model group (P < 0.05). Compared with the CP group, rice-fried group, and honey moxibustion group, the contents of ACTH and Cor in the honey moxibustion group were higher compared to those in the other two groups (P < 0.05). The content of the Na+K+-ATP enzyme in the model group was significantly higher compared to that in the control group (P < 0.05). Compared with the model group, the content of the Na+K+-ATP enzyme in the CP group, rice-fried group, and honey moxibustion group decreased significantly (P < 0.05). Compared with the CP group, rice-fried group, and honey moxibustion group, the content of the Na+K+-ATP enzyme in the honey moxibustion group was higher compared to that in the other two groups (P < 0.05). The expression of AQP1 and AQP2 mRNA in the kidney tissue of the kidney yin deficiency model group was significantly higher compared to that of the control group (P < 0 05). Compared with the model group, the expression levels of AQP1 and AQP2 mRNA in the renal tissue of rats in the CP group, rice-fried group, and honey moxibustion group decreased in different degrees (P < 0.05). There was no statistical difference between the CP group, rice stir-frying group, and honey moxibustion group. Conclusion: This study proves that the new processing method of CP can improve the endocrine physique index of rats, enhance their organ quality, and regulate the disorder of water metabolism in kidney yin deficiency syndrome and has a certain therapeutic effect on kidney yin deficiency syndrome. Different new processing methods of CP have different effects on promoting endocrine physique indexes of rats. It is concluded that honey-roasted CP has the best effect on promoting spleen deficiency, which may be through glucose metabolism, amino acid metabolism, and nucleotide metabolism, increasing ATP energy metabolism, so as to strengthen the symptoms of spleen deficiency in rats. The experimental data of this study indicate that the effect of honey-roasted CP is better compared to that of other processed products, which provides an experimental basis for the rational clinical application of the new processed products.

The synthesis of anticancer sulfonated indolo[2,1-a]isoquinoline and benzimidazo[2,1-a]isoquinolin-6(5H)-ones derivatives via a free radical cascade pathway.

A facile CuBr2 induced radical relay addition/cyclization of activated alkenes with substituted-thiosulfonates has been achieved, leading to a broad range of sulfonated indolo[2,1-a]isoquinolines and benzimidazo[2,1-a]isoquinolin-6(5H)-ones in moderate to good yields. In particular, some compounds exhibit bioactivity against cancer cell lines. This protocol shows advantages of low-cost, base-free, simple operation, and broad functional group tolerance.

Metaplastic breast carcinoma: a retrospective study of 26 cases.

Metaplastic breast carcinoma is a rare invasive breast cancer. Metaplastic breast carcinoma is mainly characterized by an epithelial or mesenchymal cell population mixed with adenocarcinoma. We collected 26 cases of metaplastic breast carcinoma in the First Affiliated Hospital of Bengbu Medical College from 2008 to 2014. Tumor size, tumor grade, vascular invasion, ER/PR status, histologic classification, and HER2/neu status were assessed for all cases and the literature was reviewed. Clinicopathologic characteristics of patients diagnosed with metaplastic breast carcinomas and its key points of differential diagnosis were discussed. All patients were female, with the median age of 50 years. The mean tumor size was 3.2 cm. 4 subtypes of metaplastic breast carcinomas were documented. Fibromatosis-like metaplastic carcinomas are typically characterized by wavy, intertwined, gentle spindle cells. When the tumor components are almost squamous cell carcinoma components and the primary squamous cell carcinoma of other organs and tissues are excluded, we can diagnose breast squamous cell carcinoma. In spindle cell carcinoma, atypical spindle cells are arranged in many ways and are usually accompanied by inflammatory cell infiltrate. Cancer with interstitial differentiation has mixed malignant epithelial and mesenchymal differentiation, and the mesenchymal components are diverse. Most tumors are triple negative. At present, surgical resection combined with chemotherapy or radiation therapy is the most effective and acceptable method for treating metaplastic breast carcinoma.

Fluorescence in situ hybridization for WWTR1-CAMTA1 has higher sensitivity and specificity for epithelioid hemangioendothelioma diagnosis.

Epithelioid hemangioendothelioma (EHE) is a rare medium-to-low-grade malignant vascular tumor characterized by vascular differentiation along with specific morphological and genetic alterations. Approximately 90% and 5% of EHE cases are associated with the WWTR1-CAMTA1 and YAP1/TFE3 fusion gene, respectively. Therefore, nuclear CAMTA1 protein expression is considered to be an effective marker for EHE diagnosis. However, the specificity and reliability of this approach have recently been put into question. The purpose of this study was to compare the detection of CAMTA1 expression in cases of EHE and histologic mimics using fluorescence in situ hybridization (FISH) and conventional protein immunohistochemistry via hematoxylin and eosin staining. Fifteen EHE and 37 histologic mimic samples were immunohistochemically stained with polyclonal anti-CAMTA1 antibody to evaluate the nuclear protein expression level of CAMTA1. In addition, 15 EHE samples and 10 vascular tumor samples were subjected to FISH to detect the WWTR1-CAMTA1 fusion gene. Histologically, EHE typically showed a mucous hyaline or cartilaginous stroma, often forming a primitive vascular lumen, and expressed vascular endothelial markers. Twelve of the 15 EHE samples showed positive nuclear CAMTA1 expression with immunohistochemistry, whereas six of the 37 histologic mimics showed positive nuclear expression. FISH detected a red-green signal fusion in 14 of the 15 cases of EHE, but in none of the 10 vascular tumors. These results indicate that CAMTA1 is an effective and useful EHE marker, but that FISH fusion gene detection has better diagnostic value and clinical significance.

The microRNA-141-3p/ CDK8 pathway regulates the chemosensitivity of breast cancer cells to trastuzumab.

AIMS: This study was conducted to explore the function of microRNA-141-3p/cyclin-dependent kinase 8 (miR-141-3p/CDK8) in regulating trastuzumab resistance of breast cancer cells. MATERIALS AND METHODS: Microarray analysis was performed to screen microRNAs that are differentially expressed in wild type and trastuzumab-resistant (TR) breast cancer cell lines. TargetScan helped predict the target gene of miR-141-3p. The regulatory relationship was confirmed through a luciferase reporter assay, quantitative reverse transcriptase polymerase chain reaction, and Western blot analysis. The MTT assay, transwell invasion assay, and wound scratch assay were performed to measure the proliferative, invasive, and migratory ability of breast cancer cells, respectively. Tumor cell xenografts in nude mice were conducted to observe the effect of miR-141-3p on trastuzumab resistance in breast cancer cells in vivo. The enzyme-linked immunosorbent assay was used to detect protein secretion. RESULTS: miR-141-3p was downregulated in the drug-resistant cell lines. CDK8 was proved to be a target gene of miR-141-3p. Transfection of miR-141-3p or CDK8 small interfering RNA (siRNA) reversed the resistance to trastuzumab in TR cell lines and suppressed cell invasion and migration. Dysregulation of transforming growth factor beta (TGF-ß) was detected when the expression of CDK8 was silenced by CDK8 siRNA, and downregulation of TGF-ß had a notable effect on reducing the phosphorylation of SMAD2/SMAD3. CONCLUSION: miR-141-3p could restore the sensitivity to trastuzumab in breast cancer cells by repressing CDK8, which might regulate the phosphorylation levels of SMAD2/SMAD3 via TGF-ß.

The correlation of the expressions of WWOX, LGR5 and vasohibin-1 in epithelial ovarian cancer and their clinical significance.

BACKGROUND: Recurrence and metastasis are the most common reasons for the treatment failure of epithelial ovarian carcinoma (EOC). WW domain-containing oxidoreductase (WWOX) is a tumor suppressor, which causes down- or lost-expression and is able to promote cell infiltration and progression in several human malignant tumors. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), an important marker of cancer stem cells (CSCs), has been considered a useful biomarker of tumor metastasis and patient prognosis. Vasohibin-1 (VASH1), also known as angiogenesis inhibiting protein-1, can be used as a biological marker for early infiltration and metastasis in many cancers. However, the correlations of WWOX, LGR5, and vasohibin-1 in EOC are still unclear. In this study, we analyzed the relationships of these three markers, as well as their respective correlations with clinicopathological characteristics, to determine whether they are useful biomarkers for the improvement and prognosis of EOC patients. METHODS: The positive rates of WWOX, LGR5, and vasohibin-1 in 210 whole tissue samples of EOC were detected by immunohistochemistry. Clinical data was also collected. RESULTS: The expressions of LGR5 and vasohibin-1 were significantly higher in EOC tissues than the levels in benign ovary tumors. However, WWOX expression was significantly lower in EOC tissues than the levels in benign ovary tumors. The investigation of the associations between WWOX, or LGR5, or vasohibin-1 positive rates with the clinicopathological characteristics of EOC showed associations between the positive rates of each with grade of tumor, lymph node metastasis (LNM), implantation, and International Federation of Gynecology and Obstetrics (FIGO) stage. The overall survival (OS) time of patients with LGR5-positive or vasohibin-1-positive EOC tissues was significantly shorter than that of those who were negative. On the contrary, the OS time of patients with WWOX-positive EOC tissues was significantly higher than the OS time of those who were negative. Importantly, a multivariate analysis indicated that the high level of WWOX, LGR5, and vasohibin-1, as well as implantation, LNM and FIGO stage could be independent prognostic biomarkers for OS in EOC patients. CONCLUSIONS: The expressions of WWOX, LGR5, and vasohibin-1 may represent useful promising biomarkers for metastasis and prognosis, as well as potential therapeutic targets in EOC.

Epithelial cell adhesion molecule and epithelial-mesenchymal transition are associated with vasculogenic mimicry, poor prognosis, and metastasis of triple negative breast cancer.

Triple-negative breast cancer (TNBC) is associated with epithelial-mesenchymal transition (EMT) and the phenotype of breast cancer stem cells (CSCs). Vasculogenic mimicry (VM) is a novel pattern of tumor blood supply and associated with aggression and metastasis of TNBC. Previous studies have shown that both CSCs and EMT are associated with VM, although the underlying mechanism is yet unclear. The present study aimed to analyze the immunohistochemical (IHC) expression of CSC marker, epithelial cell adhesion molecule (EpCAM), EMT-related markers, including transcription factors (TFs) (Slug, Twist1, and ZEB1), and EMT markers (E-cadherin and vimentin) in 137 TNBC. The expression of these markers was correlated to the clinicopathological features and VM channels of the tumors, including patient overall survival (OS) and disease-free survival (DFS). Furthermore, the expression of EpCAM and EMT-related markers showed a positive correlation with distant metastasis and lymph node metastasis (P < 0.05). A significant association was noted between VM and histological grade (P = 0.007). Moreover, VM showed a significant positive correlation with EpCAM, EMT-associated TFs, and VE-cadherin expression in TNBC. Furthermore, binary logistic analysis showed that VM expression was significantly correlated with lymph node metastasis and distant metastasis (P < 0.05). In survival analysis, the overexpression of EpCAM and ZEB1 predicted a poor prognosis with respect to OS and DFS. In addition, the presence of VM was significantly associated with poor OS and DFS. Multivariate Cox regression analysis revealed that VM expression is an independent prognostic factor for TNBC patients. In summary, VM was confirmed as a potential biomarker for TNBC associated with poor clinical outcomes and tumor metastasis. This study also suggested that EpCAM protein might be involved in VM formation by EMT in TNBC.

Primary extramammary Paget's disease: a clinicopathological study of 28 cases.

To analyze the clinical and histopathological manifestations, immunohistochemistry, treatment, and prognostic factors of primary, extramammary Paget's disease (EMPD), we systematically reviewed the clinical presentations, histopathology and follow-up courses of 28 patients with primary EMPD. Clinically, their symptoms and morphology mimicked various types of dermatoses, such as seborrheic dermatitis, eczema, candidiasis, tinea cruris and erythrasma, so the initial diagnosis of EMPD was often delayed or missed. Histopathology showed invasive EMPD, and the tumor cells were mostly solid nests or had a glandular structure. The cellular atypia was obvious and signet ring Paget's cells could usually be observed. The acantholysis phenomenon in the epidermis could be seen. The condition was associated with stromal invasion, lymphatic metastasis, and even vascular invasion. Adnexal involvement in primary EMPD was a very common feature. The immunohistochemical markers CK7, GCDFP-15, CEA and HER-2 positive can identify other tumors similar to Paget's disease. We concluded that invasive EMPD is a rare malignant skin neoplasm with morphological diversity. Poorly differentiated cell morphology, extensive adnexal involvement, and an invasive pattern of solid sheets are significantly associated with lymph node metastasis and a worse prognosis. Pathologists should be alert to invasive lesions and make the correct diagnosis.

Cervical human papillomavirus among 19 753 women attending gynecological department of a major comprehensive hospital in north Anhui China 2013-2016: Implication for cervical cancer screening and prevention.

Our study aimed to assess the prevalent, incident, and persistent infection, and clearance of HPV among 19 753 individual women attending the gynecological department at a major comprehensive hospital. HPV 16, 52, and 58 ranked top three types with the highest prevalence and incidence. The prevalence of high-risk (HR) HPV peaked among women aged 15 to 19 years, then sharply decreased with age, stabilized among women aged 25 to 44 years, and then surged again among women aged 45 years and older. HR HPV infection were more likely to be prevalent (15.9% vs 1.3%, P < 0.001), incident (17.3 vs 2.0 per 1000 person-months, P < 0.001), and persistent (33.0% vs 24.2%, P = 0.033), and less likely to clear (88 vs 115 per 1000 person-months, P = 0.040) compared to low-risk HPV types. The majority of women detected with HR HPV types did not retest within 12 months. Clinical guidelines on HPV DNA testing are needed and education and counseling about HPV infection and its implications for women detected with HPV at clinical settings are warranted.

Evaluation of the correlation of MACC1, CD44, Twist1, and KiSS-1 in the metastasis and prognosis for colon carcinoma.

BACKGROUND: Metastasis-associated in colon cancer 1 (MACC1) has been reported to promote tumor cell invasion and metastasis. Cancer stem cells and epithelial-mesenchymal transition (EMT) have also been reported to promote tumor cell proliferation, invasion, and metastasis. KiSS-1, a known suppressor of metastasis, has been reported to be down-regulated in various tumors. However, the associations of MACC1, CD44, Twist1, and KiSS-1 in colonic adenocarcinoma (CAC) invasion and metastasis remain unclear. The purpose of this study is to investigate the roles of MACC1, CD44, Twist1, and KiSS-1 in CAC invasion and metastasis and their associations with each other and with the clinicopathological characteristics of CAC patients. METHODS: Immunohistochemistry and multivariate analysis were carried out to explore the expression of MACC1, CD44, Twist1, and KiSS-1 in 212 whole-CAC-tissue specimens and the corresponding normal colon mucosa tissues. Demographic, clinicopathological, and follow-up data were also collected. RESULTS: The results of this study showed MACC1, CD44, and Twist1 expression to be up-regulated, and KiSS-1 expression was down-regulated in CAC tissues. Positive expression of MACC1, CD44, and Twist1 was found to be positively correlated with invasion, tumor grades, and lymph- node-metastasis (LNM) stages and tumor-node-metastasis (TNM) stages for patients with CAC. Positive expression of KiSS-1 was inversely associated with invasion, tumor size, LNM stage, and TNM stage. The KiSS-1-positive expression group had significantly more favorable OS than did the KiSS-1-negative group. Univariate analysis indicated that overexpression of MACC1, CD44, and Twists1 was negatively associated with longer overall survival (OS) time, and there was a positive relationship between KiSS-1-positive expression and OS time for patients with CAC. Multivariate Cox analysis demonstrated that overexpression of MACC1, CD44, Twist1, and low expression of KiSS-1 and LNM and TNM stages were independent predictors of prognosis in patients with CAC. CONCLUSIONS: The results in this study indicated that levels of expression of MACC1, CD44, Twist1, and KiSS-1 are related to the duration of OS in patients with CAC. MACC1, CD44, Twist1, and KiSS-1 may be suitable for use as biomarkers and therapeutic targets in CAC.

[Expression of AXIN and MACC1 in Gastric Carcinoma and Its Clinical Significance].

OBJECTIVE: To investigate the expression of axis inhibition protein (AXIN) and metastasis-associated in colon cancer-1 (MACC1) in gastric carcinoma and their relationship to the clinicopathologic characteristics. METHODS: Expressions of AXIN and MACC1 proteins were examined by immunohistochemistry containing 100 specimens of gastric tissues (gastric carcinoma group) and 60 specimens of normal gastric mucosa tissues (control group,the nearby tissues of the excised specimen of gastric cancer patients,from the tumor of the gastric cancer >5.0 cm,and confirm that there were no cancer cells). RESULTS: The positive rates of AXIN and MACC1 proteins in gastric carcinoma and the control tissues were 37.0% vs. 83.3% and 58.0% vs. 6.7%,respectively. The difference were significant between the two groups (both P<0.05). The expressions of AXIN and MACC1 proteins were significantly related with grades of tumor,depth of invasion,lymph node metastasis,and Duke stages ( P<0.05). Spearman analysis showed that there was a negative relationship between the AXIN expression and MACC1 expression (r=-0.355, P<0.05). Kaplan-Meier survival analysis and log-rank single factor analysis showed that AXIN and MACC1 protein expressions were related to the 5-year survival rate of patients (both P<0.05). Cox regression analysis showed that the positive expression of AXIN and the negative expression MACC1 protein,and Duke stages (Ⅲ-Ⅳ) were the independent prognostic factors of gastric carcinoma. CONCLUSION: The expressions of AXIN and MACC1 proteins are related to the prognosis of gastric carcinoma patients,and are involved in the invasion and metastasis of gastric carcinoma.

Thyroid hormone receptor interactor 13 (TRIP13) overexpression associated with tumor progression and poor prognosis in lung adenocarcinoma.

Thyroid hormone receptor interactor 13 (TRIP13) is an AAA+-ATPase that plays a key role in mitotic checkpoint complex inactivation and is associated with the progression of several cancers. However, its role in lung adenocarcinogenesis remains unknown. Here, we report that TRIP13 is highly overexpressed in multiple lung adenocarcinoma cell lines and tumor tissues. Clinically, TRIP13 expression is positively associated with tumor size, T-stage, and N-stage, and Kaplan-Meier analysis revealed that heightened TRIP13 expression is associated with lower overall survival. TRIP13 promotes lung adenocarcinoma cell proliferation, clonogenicity, and migration while inhibiting apoptosis and G2/M phase shift in vitro. Accordingly, TRIP13-silenced xenograft tumors displayed significant growth inhibition in vivo. Bioinformatics analysis demonstrated that TRIP13 interacts with a protein network associated with dsDNA break repair and PI3K/Akt signaling. TRIP13 upregulatesAktSer473 and downregulatesAktThr308/mTORSer2448activity, which suppresses accurate dsDNA break repair. TRIP13 also downregulates pro-apoptotic BadSer136 and cleaved caspase-3 while upregulating survivin. In conclusion, heightened TRIP13 expression appears to promote lung adenocarcinoma tumor progression and displays potential as a therapeutic target or biomarker for lung adenocarcinoma.

Metaplastic breast carcinoma: a clinical analysis of 26 cases.

Metaplastic breast carcinoma (MBC) is a rare and aggressive neoplasm. Morphologically, it is characterized by the presence of multiple cellular differentiation and heterologous elements (squamous cells, spindle cells, cartilage or bone, etc). The clinical significance, prognostic risk factors and optimal treatment modalities of MBC are limited. This study collected clinical and pathological data of 26 MBC cases in the First Affiliated Hospital of Bengbu Medical College from July 2002 to July 2012 and investigated the clinicopathological features and the prognosis data. All patients were females aged 34-76 years old. Median tumor size was 3.5 cm and 88.5% patients were triple-negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). MBC is associated with a poor prognosis compared with conventional invasive ductal carcinoma (IDC). In our study, 5-year Overall Survival (OS) rate and 5-year Disease-Free Survival (DFS) rate were 61.5% and 53.8% respectively. Most patients in this series had high-grade, triple-negative tumors and were treated with optimal therapy.

Aberrant expression of ALDH1, MMP9, Integrin αvß3, and KiSS-1 in invasive ductal carcinoma and their clinical significance.

BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1, a biomarker of cancer stem cells), matrix metalloproteinase 9 (MMP9, known as a matrilysin), Integrin αvß3 (known as a biomarker of cell-matrix adhesion) and KiSS-1 (suppressor gene of tumor metastasis) are all related to cancer invasion and metastasis in many cancers. The purpose of this study was to investigate the expression of ALDH1, MMP9, Integrin αvß3, and KiSS-1 in invasive ductal carcinoma (IDC), and their respective associations with clinical characteristics and survival in IDC. METHODS: Immunohistochemical staining was used to detect the expression of ALDH1, MMP9, Integrin αvß3, and KiSS-1 in 227 whole IDC tissue specimens. Patients' clinical and demographic data were both collected. RESULTS: The expression of ALDH1, MMP9, and Integrin αvß3 were significantly higher in IDC tissues than in the control tissues. The positive expressions of ALDH1, MMP9, and Integrin αvß3 were positively associated with tumor grades, lymph node metastasis (LNM), tumor stages, and tumor node metastasis (TNM) stages, and inversely with overall survival (OS) and recurrence-free survival (RFS). Positive expression of KiSS-1 was negatively associated with tumor grades, LNM, tumor stages, and TNM stages, but positively with OS and RFS. A multivariate analysis demonstrated that the positive expression of ALDH1, MMP9, Integrin αvß3, KiSS-1, ER, and HER-2, as well as TNM stages were independent prognostic factors for OS and RFS in IDC. CONCLUSIONS: The expression of ALDH1, MMP9, Integrin αvß3, and KiSS-11 should represent promising biomarkers in predicting metastasis and prognosis, as well as being potential therapeutic targets for IDC.

Fibromatosis-like metaplastic carcinoma of breast: a challenge for clinicopathologic diagnosis.

Fibromatosis-like metaplastic carcinoma of breast (FLMC) is a newly described metaplastic tumor in the (4th) edition of the WHO classification of breast tumors in 2012. It is a low-grade tumor formed by spindle cells with mild or absent nuclear atypia, embedded in collagenized stroma, and it has only <5% tumor cells showing epithelial traits. Because its biological behavior is better than that of general spindle cell metaplastic cancer, this cancer type is added to the new WHO classification. Due to their mild morphology, breast FLMCs are often misdiagnosed as benign interstitial proliferative lesions or benign mesenchymal tumors. Accurate diagnosis is a challenging task particularly in needle core biopsies. We systematically reviewed 23 cases of metaplastic breast carcinoma (MBC), 8 cases of metaplastic carcinoma with squamous cell component, 12 cases of spindle cell/sarcomatoid metaplastic carcinoma, and 3 cases of FLMC. Also, we performed CK, CK high molecular weight (34ßE12), CK7, CK5/6, P63, CD10, ER, PR, HER-2, SMA, Desmin, CD34, CD117, and S-100 immunohistochemistry, using Envision staining. This study was focused on clinical and pathological features of 3 FLMC cases and assessed the immunoprofile of MBC subtypes in a large series to improve the understanding of these diseases.

Evaluation of the correlation of vasculogenic mimicry, ALDH1, KAI1 and microvessel density in the prediction of metastasis and prognosis in colorectal carcinoma.

BACKGROUND: Metastasis and recurrence are the most common reasons for treatment failure of colorectal carcinoma (CRC). Vasculogenic mimicry (VM, blood supply formation often seen in highly aggressive tumors), Aldehyde dehydrogenase 1 (ALDH1, a biomarker of cancer stem cells), KAI1 (a suppressor gene of tumor metastasis) are all valuable factors for metastasis and prognosis in diverse human cancers. However, the correlation of VM, ALDH1, KAI1 and microvessel density (MVD) in CRC is unclear. In this study, we analyzed the correlations among VM, ALDH1, KAI1 and MVD, as well as their respective correlations with clinicopathological parameters and survival in CRC. METHODS: The level of VM, ALDH1, KAI1 and MVD in 204 whole tissue samples of CRC were examined by immunhistochemistry. Clinical data was also collected. RESULTS: Levels of VM, ALDH1 and MVD were significantly higher, and levels of KAI1 significantly lower, in CRC tissues than in normal colorectal tissues. Levels of VM, ALDH1 and MVD were positively associated with invasion of depth, lymph node metastasis (LNM), distant metastasis and tumor-node-metastasis (TNM) stages, and negatively with patients' overall survival (OS). Levels of KAI1 was negatively correlated with invasion of depth, LNM, distant metastasis and TNM stages, and the KAI1 positive expression subgroup had significantly longer OS than did the KAI1- subgroup. In multivariate analysis, high levels of VM, ALDH1 and KAI1, as well as TNM stages were independently correlated with lower OS in patients with CRC. CONCLUSIONS: VM, MVD and the expression of ALDH1 and KAI1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets for CRC.

Evaluation of the correlation of vasculogenic mimicry, ALDH1, KiSS-1, and MACC1 in the prediction of metastasis and prognosis in ovarian carcinoma.

BACKGROUND: Recurrence and metastasis are the usual manifestations of treatment failure of epithelial ovarian carcinoma (EOC). Vasculogenic mimicry (VM; blood supply development often seen in highly aggressive cancers), aldehyde dehydrogenase 1 (ALDH1, cancer stem cell biomarker), KiSS-1 (suppressor of tumor metastasis), and metastasis associated in colon cancer-1 (MACC1) are all useful predictive factors for metastasis and prognosis in various cancers. In this study, we analyzed associations among VM, ALDH1, KiSS-1, and MACC1 in EOC, and their respective correlations with clinicopathological characteristics and survival in EOC. METHODS: Positive rates of VM, ALDH1, KiSS-1, and MACC1 in 207 whole EOC tissue samples were detected by immunohistochemistry. Patients' clinical data were also collected. RESULTS: Levels of VM, ALDH1, and MACC1 were significantly higher, and levels of KiSS-1 significantly lower, in EOC tissues than in benign ovary tumors. Levels of VM, ALDH1, KiSS-1, and MACC1 were associated significantly with tumor/lymph node/metastasis (LNM) grade, implantation, and International Federation of Gynecology and Obstetrics (FIGO) stage, and with patients' overall survival (OS); whereas the KiSS-1+ subgroup had significantly longer OS than did the KiSS-1- subgroup. In multivariate analysis, high VM, ALDH1 or MACC1 levels, FIGO stage, implantation and low KiSS-1 levels were independently associated with shorter OS in patients with EOC. CONCLUSIONS: VM and expressions of ALDH1, KiSS-1, and MACC1 represent promising markers for metastasis and prognosis, and potential therapeutic targets for EOC.

Vasculogenic mimicry and expression of Twist1 and KAI1 correlate with metastasis and prognosis in lung squamous cell carcinoma.

BACKGROUND: Vasculogenic mimicry (VM) is a new blood supply development often seen in highly aggressive cancers and has been considered as a usefully metastatic and prognostic factor for many cancers. Twist1 (a biomarker of epithelial-mesenchymal transition), and KAI1 (a suppressor of tumor metastasis) are both usefully predictive factors for metastasis in many cancers. However, the metastatic and prognostic value of VM, Twist1, or KAI1 in lung squamous cell carcinoma (LSCC) is unclear. In this study, we analyzed associations among VM, Twist1, and KAI1 in LSCC, and their respective associations with clinicopathological parameters and survival in LSCC. CASE PRESENTATION: Positive rates of VM, Twist1, and KAI1 in 157 whole LSCC tissue specimens were detected by immunohistochemistry and histochemical staining. Patient's clinical data were also collected. Levels of VM and Twist1 were significantly higher, and levels of KAI1 were significantly lower, in LSCC tissues than in normal lung tissues. Levels of VM and Twist1 were positively associated with tumor grade, lymph node metastasis (LNM), and tumor-node-metastasis (TNM) stage, and inversely with patients overall survival (OS) time; levels of KAI1 was negatively associated with tumor grade, LNM, and TNM stage, and the KAI1+ subgroup had significantly longer OS time than did the KAI1- subgroup. In multivariate analysis, high VM, or Twist1 levels, TNM stage, size of tumors, and low KAI1 levels were potential to be independent prognostic factors for OS time in patients with LSCC. CONCLUSIONS: VM, and the expression of Twist1 and KAI1 represent promising markers for metastasis and prognosis, and potential therapeutic targets for LSCC.